Herpes: The relationship between time of day and infections examined in research

We are more susceptible to infection at certain times of the day as our body clock affects the ability of viruses to replicate and spread between cells, suggests new research from the University of Cambridge. The findings, published this week in the Proceedings of the National Academy of Sciences, may help explain why shift workers, whose body clocks are routinely disrupted, are more prone to health problems, including infections and chronic disease.

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When a virus enters our body, it hijacks the machinery and resources in our cells to help it replicate and spread throughout the body. However, the resources on offer fluctuate throughout the day, partly in response to our circadian rhythms – in effect, our body clock. Circadian rhythms control many aspects of our physiology and bodily functions – from our sleep patterns to body temperature, and from our immune systems to the release of hormones. These cycles are controlled by a number of genes, including Bmal1 and Clock.

To test whether our circadian rhythms affect susceptibility to, or progression of, infection, researchers at the Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, compared normal ‘wild type’ mice infected with herpes virus at different times of the day, measuring levels of virus infection and spread. The mice lived in a controlled environment where 12 hours were in daylight and 12 hours were dark.

The researchers found that virus replication in those mice infected at the very start of the day – equivalent to sunrise, when these nocturnal animals start their resting phase – was ten times greater than in mice infected ten hours into the day, when they are transitioning to their active phase. When the researchers repeated the experiment in mice lacking Bmal1, they found high levels of virus replication regardless of the time of infection.

“The time of day of infection can have a major influence on how susceptible we are to the disease, or at least on the viral replication, meaning that infection at the wrong time of day could cause a much more severe acute infection,” explains Professor Akhilesh Reddy, the study’s senior author. “This is consistent with recent studies which have shown that the time of day that the influenza vaccine is administered can influence how effectively it works.”

In addition, the researchers found similar time-of-day variation in virus replication in individual cell cultures, without influence from our immune system. Abolishing cellular circadian rhythms increased both herpes and influenza A virus infection, a dissimilar type of virus – known as an RNA virus – that infects and replicates in a very different way to herpes.